Anaplastic astrocytomas freely infiltrate tissues and trap neurons, glia, and vessels. Overall, the cellularity and degree of cytological atypia are intermediate between those of diffuse astrocytoma grade II and glioblastoma grade IV, but there is considerable inter- and intratumoral variation. Some have the cellularity of astrocytoma grade II, whereas others are as densely packed as glioblastoma. The degrees of nuclear hyperchromatism and pleomorphism also vary, from small uniform profiles to large, multilobulated forms. Cytoplasm varies in extent and conformation, from seemingly absent (cells with “naked nuclei”), to prominent and glassy (gemistocytic). While often grade III on the basis of high mitotic activity, gemistocytic astrocytomas are not, without the corroborating mitotic activity, considered grade III (anaplastic). Rare macrophage-like cell types have granular cytoplasm and generally bland nuclei (“granular cell astrocytoma”). Mitoses are required, but no specific number has been codified. In general, fewer are necessary in small specimens such those obtained by stereotactic needle biopsy. Neither vascular proliferation nor necrosis is present.

The principal histopathological features are those of a diffusely infiltrating astrocytoma with increased cellularity, distinct nuclear atypia and marked mitotic activity. The presence of microvascular glomerula or festoons and of necrotic foci reflects progression to glioblastoma and is incompatible with the diagnosis of anaplastic astrocytoma.
Regional or diffuse hypercellularity is an important diagnostic criterion. With progressive anaplasia, the nuclear morphology becomes more complex, with increasing variations in nuclear size, shape, coarseness or dispersion of chromatin, increasing nucleolar prominence and number. Additional signs of anaplasia are nuclear inclusions, multinucleated tumour cells and abnormal mitoses. Cytoplasmic variability may also increase. Gemistocytic tumour cells are often present, but rarely to an extent that would allow the diagnosis of an anaplastic gemistocytic astrocytoma. Capillaries are lined with a single layer of endothelial cells. Microvascular proliferation and necrosis are absent. Occasionally, VEGF expression and incipient microvascular proliferation are observed, but limited to occasional tumour vessels.